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Molecular subtypes and an 8-gene ketogenesis-immune prognostic signature were constructed and validated. Single-cell RNA-seq data were used to map cell-type-specific expression of prognostic genes. Functional effects of SLC2A1, a key metabolic regulator, were evaluated in A549 cells using overexpression\/knockdown approaches combined with &amp;beta;-hydroxybutyrate (BHB) treatment. A total of 135 ketogenesis-immune cross-talk genes were identified. Consensus clustering defined two LUAD subtypes with distinct prognosis and immune landscapes. Single-cell analysis revealed SLC2A1 enrichment in epithelial tumor cells. Functional assays showed that SLC2A1 overexpression enhanced proliferation, migration, glycolysis, and ATP production, whereas knockdown suppressed these processes; BHB partially rescued energy deficits in SLC2A1-deficient cells. Mechanistically, SLC2A1 regulated ketone-body utilization and AMPK\/mTOR signaling, linking metabolic reprogramming with tumor growth and immune modulation. SLC2A1 is a critical regulator of ketone-body metabolism in LUAD and serves as a potential prognostic factor.<\/p>","DOI":"10.1615\/critrevimmunol.2026062879","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T18:24:06Z","timestamp":1775154246000},"page":"59-76","source":"Crossref","is-referenced-by-count":0,"title":["SLC2A1-Dependent Ketone Metabolism Regulates Tumor Progression and Immunotherapy Efficacy in Lung Adenocarcinoma"],"prefix":"10.1615","volume":"46","author":[{"given":"Xing","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyou","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianchang","family":"Wange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"613","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. 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